Delivery device for the administration of stabilized growth promoting hormones

Abstract

The present invention relates to a delivery device designed to be implanted in an animal and for the administration of a stabilized growth promoting formulation. This device has a wall formed at least in part by a porous membrane which surrounds and defines a reservoir. The reservoir contains a growth promoting hormone and a stabilizer. Examples of such stabilizers include certain polyols, amino acids, polymers of amino acids having a charged side group at physiological pH, and choline salts.

What is claimed is: 
     
       1. A delivery device designed to be implanted in an animal and for the administration of a stabilized growth promoting formulation, said device comprising a wall, formed at least in part by a porous membrane, which surrounds and defines a reservoir containing a growth hormone and a stabilizing amount of a stabilizer which inhibits aggregation and bioinactivation of the growth hormone selected from one or more of the following: (a) a polyol selected from the group consisting of non-reducing sugars, sugar alcohols, sugar acids, lactose, pentaerythritol, water-soluble dextrans, and Ficoll;   (b) an amino acid selected from the group consisting of glycine, sarcosine, lysine or salts thereof, serine, arginine or salts thereof, betaine, N,N-dimethylglycine, aspartic acid or salts thereof, glutamic acid or salts thereof; and     (c) a choline derivative selected from the group consisting of choline chloride, choline dihydrogen citrate, choline bitartrate, choline bicarbonate, tricholine citrate, choline ascorbate, choline borate, choline gluconate, choline phosphate, di(choline) sulfate and dicholine mucate.   
     
     
       2. The delivery device of claim 1, wherein said formulation is in the form of a pellet. 
     
     
       3. The delivery device of claim 2, wherein said formulation additionally comprises a binder and a lubricant. 
     
     
       4. The delivery device of claim 3, wherein said binder is selected from the group consisting of sodium bentonite, ethyl cellulose, stearic acid, calcium stearate, adipic acid, fumaric acid, polyethylene glycol, deacetylated chitlon and cellulose acetate; and said lubricant is selected from the group consisting of magnesium stearate, sodium stearate, calcium stearate, powdered stearate acid, talc, paraffin, cocoa butter, graphite, lycopodium or combinations thereof. 
     
     
       5. The delivery device of claim 1 wherein said growth hormone is selected from the group consisting of ovine, porcine, equine, avian, human and bovine growth hormones. 
     
     
       6. The delivery device of claim 5 wherein said growth hormone is bovine growth promoting hormone. 
     
     
       7. The delivery device of claim 1 wherein said growth hormone is present in amounts of from 1 to about 97.5 percent by weight and said stabilizer is present in amounts of from 97.5 to 1 percent by weight. 
     
     
       8. The delivery device of claim 4 wherein said binder is present in amounts of from about 0.5 to about 10 percent by weight of the total weight of pellet. 
     
     
       9. The delivery device of claim 8 wherein said lubricant is present in amounts of from 5 to about 10 percent by weight of the total weight of the pellet. 
     
     
       10. A stabilized growth promoting formulation, comprising: a growth hormone, and   a stabilizing amount of a stabilizer which inhibits aggregation and bioinactivation of the growth hormone selected from one or more of the following:   (a) a polyol selected from the group consisting of non-reducing sugars, sugar alcohols, sugar acids, lactose, pentaerythritol, water-soluble dextrans, and Ficoll;   (b) an amino acid selected from the group consisting of glycine, sarcosine, lysine or salts thereof, serine, arginine or salts thereof, betaine, N,N-dimethylglycine, aspartic acid or salts thereof, glutamic acid or salts thereof; and   (c) a choline derivative selected from the group consisting of choline chloride, choline dihydrogen citrate, choline bitartrate, choline bicarbonate, tricholine citrate, choline ascorbate, choline borate, choline gluconate, choline phosphate, di(choline) sulfate and dicholine mucate.   
     
     
       11. The growth promoting formulation of claim 10, wherein said formulation is an aqueous solution comprising dissolved growth hormone and dissolved stabilizer. 
     
     
       12. The growth promoting formulation of claim 10, wherein said formulation is in the form of a dry mixture comprising solid growth hormone and solid stabilizer. 
     
     
       13. The growth promoting formulation of claim 12, wherein said formulation is in the form of a pellet. 
     
     
       14. The growth promoting formulation of claim 13, wherein said formulation additionally comprises a binder and a lubricant. 
     
     
       15. The growth promoting formulation of claim 14, wherein said binder is selected from the group consisting of sodium bentonite, ethyl cellulose, stearic acid, calcium stearate, adipic acid, fumaric acid, polyethylene glycol, deacetylated chitlon and cellulose acetate; and said lubricant is selected from the group consisting of magnesium stearate, sodium stearate, calcium stearate, powdered stearate acid, talc, paraffin, cocoa butter, graphite, lycopodium or combinations thereof. 
     
     
       16. The growth promoting formulation of claim 14 wherein said binder is present in amounts of from about 0.5 to about 10 percent by weight of the total weight of pellet. 
     
     
       17. The growth promoting formulation of claim 14 wherein said lubricant is present in amounts of from 5 to about 10 percent by weight of the total weight of the pellet. 
     
     
       18. The growth promoting formulation of claim 10 wherein said growth hormone is selected from the group consisting of ovine, porcine, equine, avian, human and bovine growth promoting hormones. 
     
     
       19. The growth promoting formulation of claim 18 wherein said growth hormone is bovine growth promoting hormone. 
     
     
       20. The growth promoting formulation of claim 10 wherein said growth promoting hormone is present in amounts of from 1 to about 97.5 percent by weight and said stabilizer is present in amounts of from 97.5 to 1 percent by weight.